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Data from Canine Oncology Study Supports Progression to Registration Studies
In September, PharmAust was also pleased to welcome Dr Michael Thurn, PhD, as Chief Executive Officer (CEO). Dr Thurn brings broad experience in drug discovery, development, regulation and commercialization acquired through leadership roles in research organisations and industry, including early-stage, fast-growing, private and publicly listed biotech companies.
PharmAust plans to use the latest trial data to open an Investigational New Animal Drug (INAD) application with the U.S. Food and Drug Administration’s (FDA) Center for Veterinary Medicine (CVM) and proceed with pivotal studies in 2024 to support product registration.
A video presentation providing further information about the Phase 2 veterinary clinical study and future directions can be watched here.
Dr Thurn compared PharmAust’s MPL tablet to the most recently approved treatment for B-Cell and T-Cell Lymphoma, LAVERDIATM, acquired in 2022 by Dechra Pharmaceuticals PLC.
“As our MPL tablet has a comparable efficacy profile to LAVERDIATM and offers significant advantages in quality of life and safety for both the dog and the owner, we are confident in the commercialisation of MPL for canine cancer,” he said.
This was a Phase 2, open-label, single-arm, dose-finding study conducted at nine sites in Australia, New Zealand and the United States. The study’s objective was to determine a clinically safe and efficacious dose of Monepantel for treating dogs with B-Cell Lymphoma whilst maintaining quality of life (QoL).
Dogs received a once-daily treatment of MPL at home for 28 days. Five separate cohorts (See Table 1 below) of dogs received different dosing regimens of MPL before a loading dose of 100 mg/kg body weight (BW) followed by a maintenance dose of 25 mg/kg was selected as the optimal dose based on efficacy and safety data.
Response to MPL therapy was assessed over 28 days following initiation of dosing of MPL. The Overall Response Rate (ORR) was defined as those dogs with Complete Response (CR; the disappearance of all evidence of disease and all lymph nodes) or Partial Response (PR; a 30% or greater decrease in the mean sum of the longest diameter of all target lesions from baseline).
The Overall Clinical Benefit (OCB) was defined as those dogs with CR, PR or Stable Disease (SD; neither sufficient decrease to qualify for PR nor sufficient increase to qualify for Progressive Disease [PD; a 20% or greater increase in the mean sum of the longest diameter of all target lesions with reference to the smallest mean sum longest diameter recorded] of all target lesions).
Time to Progression (TTP) was defined as the time from the first date of treatment to the date that the dog developed clinical or radiographic signs of PD or died from any cause, including euthanasia, and QoL was assessed by dog owners using a number ranging from 1 (very poor) to 10 (normal) on initiation of treatment (Day 0) and every day until study completion (Day 28).
Overall QoL and the following specific aspects were captured: energy level, appetite, signs of nausea or vomiting, water intake, and general Level of Function (LoF). Dog owners assessed the LoF daily using a visual analogue scale ranking between 1 (normal pet) to 4 (very weak/completely disabled)
Safety was assessed by monitoring haematological, serum chemistry and urine parameters pre-dose at baseline (Day 0), Day 14 and Day 28. Dog owners were required to document all adverse events (AEs) in the study diary. AEs were graded according to the VCOG-CTCAE v1.1.
A total of 54 dogs of mixed breeds with a median age of 8 years (range 3-13 years) and a median weight of 29.6 kg (range 6.5-87) participated in the study. The majority were neutered males (50%) and spayed females (40.4%) with late-stage disease at diagnosis (61.5% Stage IV; 28.8% Stage V) with prescapular (92.3%), popliteal (90.4%), and submandibular (78.8%) lymphomas.
Overall, treatment was regarded as safe and well-tolerated. There were no treatment-related deaths, and most of the AEs (haematological and serum chemistry) reported were mild to moderate in severity, were self-limiting and responded to supportive care. Weight loss (-0.63% to -3.37%) was minimal during the 28-day treatment period with MPL for 95% of all study dogs.
Of the 40 (14 dogs were excluded from the efficacy evaluation due to protocol violations) dogs evaluable for efficacy, PR to treatment was observed in 2 (5%) dogs, SD in 12 (30%) dogs, PD in 26 (65%) dogs confirming MPL has significant anticancer activity offering disease stabilisation. None of the dogs in this study achieved a CR. The ORR was achieved in 2 (5%) dogs. The OCB was achieved in 14 (35%) dogs, while the median TTP was 28 days. 10 (25%) dogs had a TTP >50 days, and 5 (12.5%) dogs had a TTP >80 days.
In a field effectiveness study* required for product registration, 50 evaluable dogs with B-Cell and T-Cell Lymphoma were treated with LAVERDIATM, the median TTP was 29.5 days. 17 (34%) dogs had a TTP >55 days and 3 (6%) dogs had a TTP >180 days.
Owners rated their dogs daily and recorded a score between 1 (very poor) and 10 (normal) on the owner’s diary. The median QoL score for the 43 evaluable dogs across the entire study was high at 8. In the study, 74.4% of dogs were rated >8 out of 10.
Owners rated their dogs daily by recording a score between 1 (normal pet) and 4 (very weak/dying). The median LoF score was just below normal at 1.5. No dogs were rated > 2.0.
After the Day 28 assessment, Oncologists and owners determined the next phase of therapy for dogs ending the study in sound health. In 19 of the 54 cases, a combination therapy of MPL and Prednisone was selected as the ongoing therapy.
Principal Investigator Dr Kim Agnew commented that the use of Monepantel for canine lymphoma offers disease stabilisation combined with a canine and owner safety profile which doesn’t exist currently in the therapeutic options.
“I believe as we learn more about how best to manage canine lymphoma with Monepantel with ongoing studies, dogs and owners have an option to safely medicate their dogs at home. Most importantly, the family will see their pet manage their cancer with an excellent quality of life,” he said.
The encouraging results allow PharmAust to proceed straight to registration studies for MPL as a new treatment for B-Cell Lymphoma in dogs. The Company plans to use this data to open an INAD application with the US FDA’s CVM and proceed with pivotal studies in 2024 to support product registration. The planned pivotal field studies to support product registration have been designed to incorporate feedback from potential partners and continue to proceed in parallel with business development efforts.
PharmAust Non-Executive Chairman Dr Roger Aston said, “Monepantel represents a new treatment approach for the management of B-Cell Lymphomas in dogs by eliminating the need for chemotherapy and allowing dogs to maintain an excellent quality of life for an extended period of time.”
Approximately 80% of dog owners decline treatment for various reasons, including limited access to specialised veterinary oncologists and veterinary practices that can carry out chemotherapy; concerns over the dog’s quality of life due to the often severe side effects that are a cornerstone of chemotherapy treatments; complying with the rigours of the chemotherapy regime once initiated; major safety concerns for owners who handle and/or are exposed to the chemotherapy while caring for their dog; and, the high treatment costs.
“MPL is available in tablet form allowing dogs to be treated at home, without the side effects or safety concerns for owners,” said Dr Aston.
Dr Thurn sees his appointment to the new role as “an incredible opportunity to join PharmAust at this significant point in the Company’s journey.”
“We have an exciting and maturing animal health and human pipeline, an excellent Board and world-class clinical advisors and collaborators to draw knowledge,” he said.
“I look forward to working with the Board and the team to advance PharmAust’s product pipeline.”
*Center for Veterinary Medicine (2021). Corrected Freedom of Information Summary. Application for Conditional Approval. Application Number 141-526. LAVERDIA™-CA1 verdinexor tablets. Coated Tablet Dogs. Sponsored by: Anivive Lifesciences, Inc. Date of Approval: January 11, 2021. Rockville, MD, Food and Drug Administration, Center for Veterinary Medicine. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/10270
Dr Roger Aston currently serves as Executive Chairman of PharmAust. Dr Aston brings more than 20 years experience in the pharmaceutical and healthcare industries in senior roles in the UK, Asia Pacific and Australia. He has had extensive experience on boards and as Chief Executive Officer of many private and publicly listed biotechnology companies. During his career, he has been closely involved in start-up companies and major pharmaceutical companies. Aspects of his experience include FDA and EU product registration, clinical trials, global licensing agreements, fundraising through private placements, and a network of contacts within the pharmaceutical, banking and stock broking sectors. Dr Aston holds a B.Sc. (Hons) and Ph.D. degrees from the University of Manchester from 1975 to 1981.
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